Cytoplasmic CD79a is a promising biomarker for B lymphoblastic leukemia follow up post CD19 CAR-T therapy

Abstract

Minimal residual disease (MRD) detection is an important prognostic parameter in patients with refractory or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). CD79a has been reported to exhibit a high degree of linage-specificity for B-cell differentiation, with a specificity of 88% and a sensitivity of 100%. In this study, we investigated the efficiency and prognostic role of cytoplasmic CD79a (cCD79a) antibody-gated multicolor flow cytometry (MFC) in MRD detection in patients with B-ALL who received CD19-targeted chimeric antigen receptor (CAR) T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The retrospective analysis was carried on to 59 patients who accepted allo-HSCT after CD19-CAR-T infusion from June 2016 to May 2017. The MFC MRD statuses before and after allo-HSCT were both strongly correlated with the transplantation prognosis, the MFC panel with cCD79a gating can effectively monitor MRD after CD19 CAR T-cell therapy and predict the prognosis after allo-HSCT. Trial registration: ClinicalTrials#: ChiCTR-IIh-16008711.gov: NCT03173417. Registered 30 May 2017 – retrospectively registered, https://www.clinicaltrials.gov/

Keywords:

• Chimeric antigen receptor T cells
• allogeneic hematopoietic stem cell transplantation
• refractory or relapsed B-cell lymphoblastic leukemia
• flow cytometry
• minimal residual disease

Acknowledgements

Ethics approval: All procedures were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Authors contributions

Conceptualization and funding acquisition: HW. Data curation: MC. Formal analysis: MF, AW, XZ, and JY. Investigation: MC, MF, AW, XZ, JY, YZ, XW, JZ, MG, and PL. Methodology: MC and MF. Writing-original draft: MC, MF, AW, XZ, JY, YZ, XW, JZ, MG, PL, and HW. Writing-review and editing: MC. All authors read and approved the final manuscript.

Hui Wang, corresponding author, designed the research and revise paper. Man Chen, the first author, statistical analysis, analyzed data and wrote the paper. Minjing Fu, co-first authors, gather clinical data, analyzed data and revise paper. Aixian Wang, Xueying Wu, Junyi Zhen, Meiwei Gong, Qing Du, test samples and report MRD results. Xian Zhang, Guanlan Yue, Wei Zhao, Yanli Zhao, and Peihua Lu, gather clinical data and clinical treatment.

Disclosure statement

The authors declared that they have no conflict of interest.